April 15th

In a novel approach that works around the gene defect in Wiskott-Aldrich syndrome, an inherited immune deficiency disorder, researchers used an alternative cell signaling pathway to significantly improve immune function in a 13-year-old boy with the disease. The study, at The Children's Hospital of Philadelphia, provides a proof-of-principle that immunotherapy, which harnesses elements of the body's immune system, may be used to treat this rare but often deadly disorder. "If this encouraging initial result holds up in further clinical studies, we may have a new treatment option for patients with Wiskott-Aldrich syndrome," said pediatric immunologist Dr. Jordan S. Orange, who holds the newly established Jeffrey Modell Endowed Chair in Pediatric Immunology Research at Children's Hospital. The immunotherapy study appears in the April 2011 issue of The Journal of Clinical Investigation. Wiskott-Aldrich syndrome (WAS) is a complex immunodeficiency disorder characterized by recurrent infections, eczema and thrombocytopenia (a low platelet count). Mutations in the WAS gene disable its ability to produce WAS protein (WASp), which crucially affects immune cells—particularly natural killer (NK) cells, a major component of the innate immune system. Without WASp, immune defenses are compromised, leaving WAS patients at risk for premature death from infection and cancers. This risk exists even for patients mildly affected by WAS. The only current cure for WAS is stem cell transplantation, a potentially risky procedure presently justified in severe cases. In addition, Dr. Orange recently contributed to a small experimental study of gene therapy for WAS led by European researchers, which achieved clinical benefits in two severely affected young boys.

A team led by researchers at the National Institutes of Health is the first to systematically survey the landscape of the melanoma genome, the DNA code of the deadliest form of skin cancer. The researchers have made surprising new discoveries using whole-exome sequencing, an approach that decodes the 1-2 percent of the genome that contains protein-coding genes. The study appears in the April 15, 2011, early online issue of Nature Genetics. Melanoma is the most serious form of skin cancer and its incidence is increasing more quickly than that of any other cancer. A major cause is thought to be overexposure to the sun, particularly ultraviolet radiation, which can damage DNA and lead to cancer-causing genetic changes within skin cells. "It is now clear that genomic analysis will have a major impact on our ability to diagnose and treat cancer," said National Human Genome Research Institute Director Dr. Eric D. Green, who was not involved in the study. "This study represents a collaboration of basic science, clinical research, genome sequencing, and data analysis at its best." The researchers conducted a comprehensive genome analysis and explored the melanoma genome's functional components, especially gene alterations, or mutations. They studied advanced disease — the metastatic stage — when cells have the highest accumulation of gene mutations. "Melanoma is one of the most challenging solid cancers to work with because it has such a high rate of mutation," said senior author Dr. Yardena Samuels, investigator in the Cancer Genetics Branch of the NHGRI's Division of Intramural Research.

Insects use their antennae for smelling and thus for locating resources in their environment. Max Planck researchers now present the first complete analysis of genes involved in antennal olfaction of the tobacco hornworm Manduca sexta. Approximately 70 different receptors expressed in some 100 000 neurons allow these moths to detect a large number of odors and to perform odor-guided behaviors. This is the first essentially complete antennal transcriptome characterized in a non-model insect. Insects have a highly sensitive sense of smell. Extremely low concentrations of odor molecules in the air are sufficient to be detected by receptor neurons on their antennae. Specific proteins, so-called receptor proteins, expressed in these neurons recognize the odors. The odor molecules bind to the receptors and produce chemical and electrical signals that are processed in the insect brain and eventually affect the insect's behavior. Apart from the receptors, further proteins involved in olfaction, including enzymes and chemosensory proteins, come into play. Based on these molecular principles, all insects follow their innate and elementary survival formula: finding food, recognizing mates, and − in the case of females − identifying adequate oviposition sites that guarantee nutritious and easily digestible food for their offspring. Moths are popular research objects in addition to fruit flies. The genome of the silkworm Bombyx mori has been fully sequenced; however, this insect has been domesticated by humans for thousands of years, therefore its native conspecifics cannot be found anymore.

A safer and more effective treatment for 10 million people in developing countries who suffer from infections caused by trypanosome parasites could become a reality thanks to new research from Queen Mary, University of London published in the April 15 issue of the Journal of Biologicasl Chemistry. Scientists have uncovered the mechanisms behind a drug used to treat African sleeping sickness and Chagas disease, infections caused by trypanosome parasites which result in 60,000 deaths each year. The study investigated how the drug nifurtimox works to kill off the trypanosome. Co-author of the study, Dr. Shane Wilkinson from Queen Mary's School of Biological and Chemical Sciences, said: "Hopefully our research will lead to the development of anti-parasitic medicines which have fewer side effects than nifurtimox and are more effective. "What we've found is that an enzyme within the parasites carries out the process nifurtimox needs to be converted to a toxic form. This produces a breakdown product which kills the parasite. "This mechanism overturns the long-held belief that nifurtimox worked against the parasites by inducing oxidative stress in cells." Nifurtimox has been used for more than 40 years to treat Chagas disease (also known as American trypanosomiasis) and has recently been recommended for use as part of a nifurtimox-eflornithine combination therapy for African sleeping sickness (also called human African trypanosomiasis). Dr. Wilkinson and his colleagues Dr. Belinda Hall and Mr. Christopher Bot from Queen Mary's School of Biological and Chemical Sciences focused their research on the characterization of the breakdown product from nifurtimox. "The backbone of nifurtimox contains a chemical group called a nitro linked to a ring structure called a furan," Dr. Wilkinson explained.

April 12th

Researchers have found that the tiger-parrots of New Guinea‘s rainforests – named for their striped or barred plumage – are not, as has been widely accepted, closely related either to a group of rosella-like parrots found in Australia and Oceania, nor a similar group found in Asia and Africa. In press in Molecular Phylogenetics and Evolution, the scientists report that tiger-parrots instead occupy their own perch on the parrot evolutionary tree. Co-author, the Director of CSIRO’s Australian National Wildlife Collection (ANWC) Dr. Leo Joseph, said the findings will help improve our understanding of how parrots have evolved. “This research on tiger-parrots – and some other enigmatic Australian parrots such as the little-known Night Parrot of inland Australian deserts – sheds light on the bigger picture of parrot evolution for Australia and New Guinea,” Dr. Joseph said. “It has shown for the first time, for example, that tiger-parrots represent a very early branch of the parrot evolutionary tree in Australia and New Guinea. “The research team’s quest has been to understand the true places of parrots such as the Night Parrot and the tiger-parrots in the ecological and evolutionary history of parrots across the Australian continent. “During our research on these oddball parrots of Australia and New Guinea, we affirmed that the Australian parrots are far from one cohesive group. They appear, instead, to be made up of about five different main branches of the parrot evolutionary tree,” Dr Joseph said. “We have shown that the New Guinea tiger-parrots aren’t rosella-like parrots and that their resemblance in some aspects of their appearance to rosellas probably indicates some plumage characters that have been part of the evolution of parrots of Australia and New Guinea for a long time.

Just as monarch butterflies depend on circadian cues to begin their annual migration, so do plants to survive freezing temperatures. All living things – humans, animals, plants, microbes – are influenced by circadian rhythms, which are physical, mental and behavioral changes that follow a 24-hour cycle. In the April 6, 2011 online edition of PNAS, Dr. Michael Thomashow, University Distinguished Professor of molecular genetics, along with MSU colleagues Dr. Malia Dong and Dr. Eva Farré, has identified that the circadian clock provides key input required for plants to attain maximum freezing tolerance. “The integration of cold-signaling pathways with the circadian clock may have been an important evolutionary event that has contributed to plant adaptation to cold environments,” Dr. Thomashow said. Dr. Thomashow, who is an elected member of the National Academy of Sciences for his contributions to the field of plant biology, has focused his research on the identification of stress response pathways involved in freezing and drought tolerance. Stresses, including extreme temperatures and water deficit, are major factors that limit the geographical locations where food and potential bioenergy crops can be grown. His research led to the identification of the C-repeat binding factor, or CBF response pathway, a stress pathway that can be found in many different plants and plays a major role in freezing and drought tolerance. Reducing abiotic stresses, such as extremes in temperature and drought, can help expand where crops can be grown and increase yields on an annual basis, Dr. Thomashow said.

April 12th

Squamous cell cancers of the oral cavity and esophagus are common throughout the world, with over 650,000 cases of oral cancer each year and esophageal cancer representing the sixth most common cause of cancer death in men. Research by University of Pennsylvania School of Medicine investigators has shown that a protein that helps cells stick together is frequently absent or out of place in these cancers, but it's unclear if its loss causes the tumors. The investigators report that mice engineered to lack this protein, called p120-catenin (p120ctn), in the oral-upper digestive tract develop squamous cell cancers. The data, reported in the April 12, 2011 issue of Cancer Cell, settles a 20-year debate and proves that p120ctn is a tumor-suppressor protein. What's more, the tumors that form in this mouse model closely resemble human disease and may point the way to novel therapies and early detection strategies. "As the mice aged, what we saw was a dramatic evolution of precancer to cancer," says senior author Dr. Anil K. Rustgi, the T. Grier Miller Professor of Medicine and Genetics and chief of Gastroenterology. "Both the precancerous growth, called dysplasia, and the cancer look exactly like what we see in humans. This is really exciting because it supports efforts for prevention and early detection, especially in people who drink alcohol and smoke cigarettes excessively and are at high risk for the disease in many regions of the world." In healthy tissues, p120ctn is part of a protein complex that holds epithelial cells in tightly packed sheets. When p120ctn (or another of these cell adhesion proteins) is lost, a wide variety of cancers, including those in prostate, breast, pancreas, colon, skin, bladder, and the endometrium, can result.

The discovery of two genes that encode copper- and sulfur-binding repressors in the hospital terror Staphylococcus aureus means two new potential avenues for controlling the increasingly drug-resistant bacterium, scientists say in the April 15, 2011 issue of the Journal of Biological Chemistry. "We need to come up with new targets for antibacterial agents," said Indiana University Bloomington biochemist Dr. David Giedroc, who led the project. "Staph is becoming more and more multi-drug resistant, and both of the systems we discovered are promising." The work was a collaboration of members of Giedroc's laboratory, and those of Vanderbilt University School of Medicine infectious disease specialist Dr. Eric Skaar, and University of Georgia chemist Dr. Robert Scott. MRSA, or multidrug-resistant Staphylococcus aureus, is the primary cause of nosocomial infections in the United States. About 350,000 infections were reported last year, about 20 percent of which resulted in fatalities, according to the Centers for Disease Control. One to two percent of the U.S. population has MRSA in their noses, a preferred colonization spot. One of the repressors the scientists discovered, CsoR (copper-sensitive operon repressor), regulates the expression of copper resistance genes, and is related to a CsoR previously discovered by the Giedroc group in Mycobacterium tuberculosis, the bacterium that causes tuberculosis in humans. When the bacterium is exposed to excess copper, the repressor binds copper (I) and falls away from the bacterial genome to which it is bound, making it possible for the copper resistance genes to be turned on.

A study published by two University of Iowa researchers in the March 31, 2011 issue of the Journal of Vision found that pigeons recognize a human face's identity and emotional expression in much the same way as people do. Pigeons were shown photographs of human faces that varied in the identity of the face, as well as in their emotional expression -- such as a frown or a smile. In one experiment, pigeons, like humans, were found to perceive the similarity among faces sharing identity and emotion. In a second, key experiment, the pigeons' task was to categorize the photographs according to only one of these dimensions and to ignore the other. The pigeons found it easier to ignore emotion when they recognized face identity than to ignore identity when they recognized face emotion, according to Dr. Ed Wasserman, Stuit Professor of Experimental Psychology, and graduate student Fabian Soto, both of the UI College of Liberal Arts and Sciences Department of Psychology. "This asymmetry has been found many times in experiments with people and it has always been interpreted as the result of the unique organization of the human face processing system." Soto said. "We have provided the first evidence suggesting that this effect can arise from perceptual processes present in other vertebrates. The point of the project is not that pigeons perceive faces just as we do or that people do not have specialized processes for face perception. Rather, the point is that both specialized and general processes are likely to be involved in peoples' recognition of faces and that the contributions of each should be carefully determined empirically," he added. In fact, the findings could make scientists reconsider their assumptions about how uniquely human cognitive processes might interact with more general processes in complex tasks such as face recognition.

For the first time in a human model, scientists have discovered how anti-depressants make new brain cells. This implies that researchers can now develop better and more efficient drugs to combat depression. Previous studies have shown that anti-depressants make new brain cells, however, until now it was not known how they did it. In a study published online on April 12, 2011, in the journal Molecular Psychiatry, researchers from the Institute of Psychiatry, King's College London, show that anti-depressants regulate the glucocorticoid receptor (GR) - a key protein involved in the stress response. Moreover, the study shows that all types of anti-depressant are dependent on the GR to create new cells. Depression is expected to be the second leading burden of disease worldwide by the year 2020. Recent studies have demonstrated that depressed patients show a reduction in a process called ‘neurogenesis,’ that is, a reduction in the development of new brain cells. This reduced neurogenesis may contribute to the debilitating psychological symptoms of depression, such as low mood or impaired memory. With as much as half of all depressed patients failing to improve with currently available treatments, developing new effective anti-depressant treatment still remains a great challenge, which makes it crucial to identify new potential mechanisms to target. The Laboratory of Stress, Psychiatry and Immunology (SPI-lab) at King's has been looking into the role of the GR in depression for a number of years. In this study, scientists used human hippocampal stem cells, the source of new cells in the human brain, as a new model to investigate, 'in a dish,' the effects of anti-depressants on brain cells.